Repeat Administration of Reversal Agents in Patients Receiving Neostigmine or Sugammadex: A Retrospective Observational Study

Abstract Background: Antagonism of neuromuscular blockade (NMB) induced by rocuronium and vecuronium can be achieved with either neostigmine or sugammadex. Compared to sugammadex, antagonism with neostigmine is more likely to result in incomplete reversal, i.e. residual neuromuscular blockade (rNMB). The administration of additional doses of a reversal agent following an initial reversal dose may be a marker for suspected rNMB. We studied the frequency and temporal patterns of repeat (rescue) administration of reversal agents in patients who received an initial dose of neostigmine vs. sugammadex. Methods: We analyzed retrospective data from electronic anesthesia records to identify surgical patients who received rescue dose reversal, defined as two or more doses of reversal agent, following administration of non-depolarizing NMB and extubation in the operating room. We assessed rates of rescue reversal over time following the introduction of sugammadex and compared rescue rates for patients receiving neostigmine vs sugammadex. Results: A total of 24,027 cases using cisatracurium, rocuronium, and vecuronium were analyzed. Following the addition of sugammadex to formulary in 2016, reversal with neostigmine decreased from 79% to 5.3% (p <0.001) and the use of rescue reversal after neostigmine increased from 6.0% to 18% (p<0.001). In contrast, rescue reversal after sugammadex was 2.5%, with no change over the study period (p=0.059). The percentage of patients who were not given any reversal agent following non-depolarizing NMB decreased from 20% to 13% (p<0.001). As neostigmine usage progressively decreased after introduction of sugammadex, there was a corresponding increase in rescue reversal dosing when initial reversal was attempted with neostigmine. Conclusions: Repeated administration of a reversal agent was 7 times more likely to occur in patients initially reversed with neostigmine compared to sugammadex. This finding likely reflects increased rates of observed weakness in patients reversed with neostigmine. The correlation between decreasing neostigmine use and increasing rescue reversal after neostigmine may indicate a progressive decline in the effective use of neostigmine (as knowledge and experience waned), and/or decreasing confidence in its efficacy.